We plan to continue our studies on the metabolism of gastrin, the mechanisms by which gastrin is released and degraded and the actions and interactions of gastrin with other hormones. We plan to study the concentration of gastrin in the fundus, antrum, segments of the duodenum, segments of the jejunum and ileum and by radioimmunoassay and chromatographic methods to characterize the forms of gastrin in different divisions of the stomach and gastrointestinal tract. We plan to investigate the mechanisms by which acidification of the duodenum effects gastrin release, gastric acid output and pancreatic output. We plan to determine if antibodies to gastrin can suppress gastric acid output and thereby be used to treat patients with duodenal ulcer disease and Zollinger-Ellison syndrome. We plan to study the effects of various chemical agents on gastrin release and gastric acid output and the mechanisms by which these agents act to stimulate or suppressgastrin and/or gastric acid in experimental animals and man during different physiologic and pathologic states. We plan to study the temporal pattern of release of cholecystokinin and by a radioimmunoassay method, determine the disappearance half-time of endogenous cholecystokinin from the circulation of experimental animals. We plan to use radioimmunoassay and chromatographic methods to investigate the molecular forms of gastrin in the circulation of man and experimental animals during basal, stimulated and suppressed states and in dogs to determine the relative concentrations of the different forms of gastrin after transit through various organs (liver, kidney and small bowel). We intend to develop and validate radioimmunoassays for measuring the concentration of secretin, glucagon, VIP and GIP in tissues and body fluids of man and experimental animals. These assay systems will be used to study the mechanisms of actions and interactions of hormones of gastrointestinaland pancreatic origin.